- Title
- Development and characterisation of miconazole nitrate loaded solid lipid nanoparticles for incorporation into a vaginal mucoadhesive system
- Creator
- Gwimo, Wimana Alexis
- Subject
- Vaginitis
- Subject
- Vagina -- Diseases Sexually transmitted diseases -- Diagnosis Sexually transmitted diseases -- Treatment
- Date Issued
- 2019
- Date
- 2019
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- http://hdl.handle.net/10948/39632
- Identifier
- vital:35335
- Description
- Vulvovaginal candidiasis (VVC) is the second most common cause of vaginitis, affecting 75% of women of sexual maturity. The prescribed first line treatment involves the use of locally-acting imidazole creams. These conventional dosage forms possess limitations, such as leakage, messiness and low residence time at the site of application; all which promote poor patient adherence to pharmacotherapy. Poor adherence is then attributed to increased incidence of VVC reoccurrence and the emergence of Candida strains. It was, therefore, speculated that through the use of novel drug delivery systems (NDDS), the pharmacokinetic and antimicrobial characteristics of a model antifungal drug (miconazole nitrate [MNZ]) could be improved. Primary aim: To develop, optimise and characterise a mucoadhesive hydrogel incorporated with MNZ loaded solid lipid nanoparticles (MNZ-SLNs) for the intended treatment of VVC. This study was conducted in three phases, viz. pre-formulation studies, development, optimisation and characterisation of MNZ-SLNs, and the development and characterisation of MNZ-SLN-loaded thermoresponsive hydrogel. An alternative method for the quantification of MNZ was developed through the use of an octyl stationary phase. The method was deemed suitable for its intended use with a linear equation of y = 811214x + 67958 and a respective limit of quantitation (LoQ) and detection of 0.015 mg/ml and 0.052 mg/ml. Differential scanning calorimetry (DSC) studies suggested that cholesterol showed great promise of facilitating high drug entrapment efficiency (EE). MNZ-SLNs were prepared by means of a novel melt- emulsification sonication and low temperature solidification method and optimised statistically by a 13-run-two-factor central composite rotatable design (CCRD). The predicted optimisation parameters were 4% m/v lipid concentration and 260.94 sonication time. Optimal MNZ-SLN formulations were prepared and characterised by means of photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and centrifugation. PCS revealed uniform particles with a narrow polydispersity index (PDI) and a mean hydrodynamic diameter (z-avg.) of 73.03 nm and zeta potential (ZP) of 38.43 mV. Percent EE was calculated via an indirect method as 75.24%. Furthermore, the MNZ -SLNs were incorporated into a mucoadhesive thermo-responsive hydrogel with a sol-gel transition temperature of 33.33 ± 2.82 °C. In vitro drug release testing (IVDRT) was undertaken with the aid of a Franz diffusion vertical cell (FDVC) apparatus. A % cumulative drug release of 27.94% and 15.87% was obtained for MNZ- SLNs and MNZ-SLN hydrogels, respectively, after eight hours. The resultant data was fitted into various kinetic models with the aid of DDSolverTM (Microsoft Excel® add-ins, 2016) to evaluate which model attained the highest correlation co-efficient (r2). Both formulations attained high r2 of 0.9941 and 0.9945, respectively, with the Korsmeyer- Peppas mathematical model. A high diffusional exponent (n) of >1 was observed, suggesting a super case II drug release mechanism. Finally, a modified Kirby-Bauer disc diffusion assay was used for ascertaining Candida albicans susceptibility to the developed formulations. Controls in the form of unloaded preparations and a commercially available cream were used. MNZ-SLNs and MNZ-hydrogel demonstrated superior antifungal activity to the commercially available cream. These results indicate that the developed MNZ-SLNloaded hydrogel formulation with localised thermo-responsive effect may be a promising carrier for intravaginal delivery of MNZ in the treatment of VVC.
- Format
- xxxi, 268 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Health Sciences
- Language
- English
- Rights
- Nelson Mandela University
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | WIMANA ALEXIS GWIMO.pdf | 4 MB | Adobe Acrobat PDF | View Details Download |